Morpholino-substituted-2-aminobenzophenomimines

ABSTRACT

DISCLOSED ARE COMPOUNDS OF THE CLASS OF MORPHOLINOSUBSTITUTED 1-SUBSTITUTED-4-ARYL-2(1H)-QUINAZOLINONES USEFUL AS PHARMACEUTICAL AGENTS, E.G., AS ANTI-INFLAMMATORY AGENTS.

United States Patent Oflice Patented June 25, 1974 2(lH)-quinazolinone of the formula II with a compound 3,819,625 of formula IIA, as illustrated as follows: MORPHOLINO-SUBSTITUTED-2-AMINOBENZO- PHENOMIMINES Hans Ott, Basel-Land, Switzerland, assignoi' to Xcmcmocmcmx Sandoz, Inc., Hanover, NJ. 5 :0

No Drawing. Original application Aug. 13, 1969, Ser. No. 1,

849,863, now Patent No. 3,642,791. Divided and this application Sept. 1, 1971, Ser. No. 177,154 R 1 Int. Cl. C07d 87/40 R (II) US. Cl. 260-247.5 R Claims 10 N ABSTRACT on THE DISCLOSURE o o Disclosed are compounds of the class of morpholino- N substituted 1-substituted-4-aryl-2(1H)-quinazolinones usc- R ful as pharmaceutical agents, e.g., as anti-inflammatory (D agents.

wherein R, R and R" are as above defined, and X is chloro or bromo, and thus more particularly involves This application is a division of Ser. No. 849,863, filed subjecting said compound II to reaction with a bis(2-halo- Aug. 13, 1969, now US. Letters Patent No. 3,642,791. ethyl)ether in the presence of an acid acceptor of known This invention relates to bicyclic compounds. In partictype which is otherwise non-reactive with compound II, ular, the invention relates to 1-substituted-4-aryl-2(1H)- e.g., an alkali metal carbonate or tertiary amine, to form quinazolinones having a morpholino substituent in the the compounds of the invention of formula I. This reacbenzene portion of the quinazoline ring, and to methods tion is carried out at elevated temperatures of from 100 of preparing the same. The invention also relates to phar- C. to 200 C., preferably at 100 C. to 170 C. and prefmaceutical compositions and methods employing said suberably using the bis(2-bromoethyl)ether in excess as a stituted quinazolinones. solvent. Other inert solvents may be also employed. The

The quinazolinones of the invention may be represented reaction product of formula I may be isolated from the by the formula I: reaction mixture of Procedure A by working up by estao lished procedures. m If The second preferred process, referred to herein as N Procedure B, involves the cyclization-reaction between an appropriately substituted morpholino-o-aminobenzo- N phenonimine of formula III and phosgene and may be illustrated as follows:

I I R i" I 6 N 6 N wherein I phosgene 0 R represents hydrogen; halo, preferably of atomic weight NE N no greater than 80; lower alkyl, preferably containing B y R I 1 to 3 carbon atoms; or lower alkoxy, preferably con- H R taining 1 to 2 carbon atoms; (III) (I) R represents lower alkyl, preferably containing from 1 to 5 carbon atoms, e.g., methyl, ethyl, propyl, isopro- H pyl, butyl, sec-butyl and isobutyl; allyl, methallyl, or Y R and R are as above definedpropargyl; tion of compounds of formula I by Procedure B involving R" represents phenyl, or substituted phenyl of the forh reactlon of compoun? In Wlth Phosgene may be mula: 5 ried out at temperatures in the range of 0 C. to C.,

preferably 10 C. to 30 C. The reaction is desirably car- Y ried out in an inert organic solvent which may be any of several convenient for the purpose, preferably an aro- Q matic hydrocarbon, e.g., benzene, toluene, and xylene, more preferablybenzene. The mole ratio of phosgene to compound III is not particularly important and a substanwhel'em tial excess of phosgene is employed in the preferred forms Y represents halo of atomlc Welght f greater than of practice to obtain more efficient reaction rates. In a pre- 80; lower alkyl: Pmferably contammg from 1 to ferred embodiment of the invention, the cyclization reac- 3 Carbon 9 1 8-, y lower alkoxy, P tion is carried out in the presence of an acid acceptor of erably contaimng from 1 to 2 carbon atoms, e.g., 6 known type which may be either an inorganic base or methoxy; or trifluol'omethyl; and organic base, e.g., triethylamine. The compounds of forrepresents hydrogen; halo of atomlc mula I may be isolated from the reaction mixture of Progreater than 80; lower alkyl, preferably containing cedure B by working up by conventional techniques from 1 to 3 carbon atoms, e.g., methyl; or lower The compounds f fo mula II employed as starting matealkoxy Preferably containing from 1 to 2 carbon rial in Procedure A may be prepared as described in coamms, meflmy pending application Ser. No. 775,201 filed Nov. 12, 1968, or a non-toxic pharmaceutically acceptable acid addition now US. Letters Pat. 3,723,432, and preferably by reducsalt thereof. tion in a known manner of the corresponding nitro sub- A first preferred process for preparation of the comstituted 4-aryl-2(IHl-quinazolinone as described in said pounds I and referred to herein as Procedure A, involves 7 application. The said nitro substituted 2( 1H)-quina zothe reaction of an appropriately substituted amino-4-aryllinones are also prepared as described in said application by one or more procedures including, for example, the cyclization of a nitro substituted 2-alkylaminobenzophenone with urethane in the presence of zinc chloride at temperatures of 160 C. to 200 C.; the nitration of an appropriately substituted l-substituted 4 aryl-2(1H)- quinazolinone; and the cyclization of a nitro substituted 2- alkylaminobenzophenonimine with phosgene.

The compounds of formula III employed as starting material in Procedure B are novel compounds and are preferably prepared by a Step 1 reaction involving reacting a compound of the formula IV:

in which R and R are as defined, with a compound of the formula V:

Q I! V in which R" is as defined and Q is lithium or MgX wherein X is iodo, chloro or bromo, in an inert organic solvent.

The preparation of compounds III by Step 1 involving reaction of a compound IV and compound V maybe carried out at temperatures in the range C. to 40 0, preferably 5 C. to 25 C. and in an inert medium which may be provided by any of several organic solvents of known type for such reactions, preferably an ether such as diethyl ether, tetrahydrofuran and dioxane. The preferred compound V is a phenyl lithium compound.

The compounds of formula IV employed as starting material in preparation of compounds III are novel compounds but may be prepared employing procedures and sequences known in the art for preparation of 2-alkylaminobenzonitriles as modified or supplemented by the disclosure herein. A multi-step procedure for purposes of illustration involves the reaction in a Step 2 of a compound of the formula VI:

HZN No:

R Hal with the bis(2-haloethyl)ether to obtain a compound of the formula VII:

R Hal VII wherein R is as defined and Hal indicates chloro or bromo, said compound VII then being reacted in a Step 3 with cuprous cyanide to obtain a compound of formula VIII:

VIII

wherein R is as defined, said compound VIII then being subjected in a Step 4 to reduction in a known manner to obtain a compound IX:

The reaction of Step 3 is suitably carried out at elevated temperatures and in the presence of an organic solvent, which is inert under the reaction conditions. The reaction temperature may, for example, range from about C. to 220 C. and preferably C. to 180 C. The preferred solvents are solvents boiling within the preferred range of reaction temperatures in order that reflux conditions may be employed, e.g. dimethylacetamide and dimethylformamide, more preferably dimethylacetamide. The mole ratio of cuprous cyanide to compound of formula VII in the reaction mixture is not particularly critical and typically ranges from approximately the stoichiometric amount required to form the desired product up to a moderate excess. The reaction time is typically about 1 to 10 hours. The Hal in the compound of formula VII is preferably a chlorine atom. The decomposition of the resulting cuprous complex may, for example, be effected by addition of methylene chloride, and the resulting product isolated for use by known procedures.

The reduction reaction of Step 4 may be effected according to any of several well-known procedures. Preferably, the reduction is carried out in an aqueous acidic medium employing a reducing metal of which illustrative examples include iron, zinc and tin, preferably iron. Suitable acids include hydrochloric acid and acetic acid, preferably hydrochloric acid. The reduction is preferably effected at a temperature of from 50 C. to 100 C. and in a solvent which is inert under the reaction conditions. Suitable solvents include water and lower alkanols, especially ethanol, and combinations thereof. An alternate known method of reduction involves catalytic hydrogenation in a known manner, employing Raney nickel, palladium or platinum as catalyst, and a convenient organic solvent, for example, methanol, ethanol or dioxane.

The alkylation reaction of Step 5 employed in producing compounds of formula IV may be carried out by known procedures involving tosylation, alkylation and detosylation of compounds IX. The compounds IV in which R' is branch chain alkyl and the branching occurs on the carbon atom attached directly to the nitrogen atom, e.g. an 2-isopropylaminobenzonitrile, are, however, preferably prepared by reaction of a compound of formula IX with an alkyl halide of formula X:

XR X

in which X is bromo or iodo and R is a branched alkyl of the type above-indicated. The reaction of a compound IX with a compound X is exemplified hereinafter and may be generally carried out analogously to the similar procedures described in the above-mentioned application Ser. No. 775,201.

It will also be evident that the particularly preferred procedure for preparation of a compound of formula (I) will vary depending on one or more of several known factors including the particular compound desired, availability of starting materials and apparatus, cost and the like. In the usual case, the above-described Procedure B is usually preferred for preparation of compounds (I) in which the morpholino substituent is to be placed at the 6-position of the quinazolinone product, e.g., for example, this route of synthesis was used to obtain l-isopropyl-6-morpholino 4 phenyl-2( lI-I)-quinazolinone in Example 2 of this application. Procedure A is usually more suitable for preparation of compounds (I) in which the morpholino substituent is placed at other than the 6-position, e.g., this route of synthesis was used to obtain l-isopropyl-7-morpholino 4 phenyl-2(1H)- quinazolinone in Example 1 of this application. Procedure B is used for R' =tert.alkyl.

Also within the scope of the novel compounds provided by the invention are pharmaceutically acceptable salts not materially affecting the pharmacological effect of the compounds of formula (1). Such salts include the acid addition salts, e.g., the hydrochloride, which is mentioned for purposes of illustration only. The acid addition salts may be produced as desired from the corresponding free bases by conventional procedures. Conversely, the free bases may be obtained from the salts by procedures known in the art.

The compounds of structural formula I are useful because they possess pharmacological activity in animals. In particular, the compounds are useful as anti-inflammatory agents as indicated by the carrageenin-induced edema test on rats (oral administration). For such use, the compounds may be combined with a pharmaceutically acceptable carrier, and such other conventional adjuvants as may be necessary, and administered orally in such forms as tablets, capsules, elixirs, suspensions and the like or parenterally in the form of an injectable solu tion or suspension. The dosage administered will, 01 course, vary depending upon the compounds used and the mode of administration. However, in general, satisfactory results are obtained when administered at a daily dosage of from about 0.3 milligrams to about 150 milligrams per kilogram of body weight, preferably given in divided doses 2 to 4 times a day, or in sustained release form. For most mammals the administration of from about 20 milligrams to about 1000 milligrams of the compound per day provides satisfactory results and dosage forms suitable for internal administration comprise from about 5 milligrams to about 500 milligrams of the compound in admixture with a solid or liquid pharmaceutical carrier or diluent.

The compounds I of the invention are also useful as analgesics as indicated by application of pressure to yeast-inflamed foot of the rat (oral administration). For such use, the compound may be administered to obtain satisfactory results at dosages and in modes similar to those employed in the treatment of inflammation.

A representative formulation is a tablet prepared by conventional tabletting techniques and containing the following ingredients:

Ingredient Parts by weight 6-morpholino-l-isopropyl 4 phenyl-2(1H)- quinazolinone 50 Tragacanth 2 Lactose 39.5 Corn starch 5 Talcum 3 Magnesium stearate 0.5

As is often the case with compounds exhibiting antiinflammatory and analgesic activity, compounds I within the scope of the invention also exhibit anti-bradykinin activity as demonstrated on intravenous administration to the guinea pig, for example, in doses of 4.0 to 5000 micrograms per kilogram of body weight.

The following examples show representative compounds encompassed within the scope of this invention and the manner in which such compounds are prepared. However, it is to be understood that the examples are for purposes of illustration only.

. EXAMPLE 1 1-isopropyl-7-morpholino-4-phenyl-2( 1H) -quinazolinone CH3 CH:

Step A.Preparation of 4-morpholino-Z-nitro-chlorobenzene: A mixture of 50 g. of 4-chloro-3-nitr0aniline and 50 g. of anhydrous potassium carbonate in 200 ml. of bis- (2-bromoethyl)ether is stirred and heated at 160 C. for 6 hours. The resulting dark mixture is coo-led to room temperature and diluted with 500 ml. of methylene chloride. The inorganicsolid is removed by filtration and the filtrate is concentrated to dryness to yield a crude residue which is crystallized from ethanol to obtain 4-morpholino- 2-nitro-chlorobenzene, M.P. 104 C. to 105 C.

Step B: Preparation of 2-cyano-S-morpholino-nitrobenzene: A mixture of 43 .g. of 4-morpholino-2-nitrochlorobenzene and 20 g. of cuprous cyanide in ml. of dimethylacetamide is stirred and heated under reflux for 8 hours. The resulting dark brown solution is cooled and concentrated in vacuo. The residue is distributed between methylene chloride and water made basic with ammonium hydroxide. The organic phase is separated and first washed with about 2N ammonium hydroxide and then with water. After drying the methylene chloride is removed in vacuo to yield a residue which is crystallized from ethyl acetate to obtain 2-cyano-5-morpholinc-nitrobenzene, m.p. 192 C. to 194 C.

Step C.Preparation of 2-cyano-S-morpholino-aniline: To a refluxing mixture of 10 g. of 2-cyano-5-morpholinonitrobenzene in 100 ml. of ethanol, 20 ml. of dioxane and 30 ml. of concentrated hydrochloricacid is added 5 g. of iron powder in portions. When the addition is complete the mixture is refluxed for 30 minutes. It is then filtered hot through Celite and the filtrate is concentrated to dryness in vacuo. The residue is distributed between methylene chloride and 2N sodium hydroxide solution. The organic phase is separated and washed twice with a saturated solution of sodium chloride. After drying, the methylene chloride is removed in vacuo and the residue is crystallized from ethanol to obtain Z-cyano-5-morpholino-aniline, m.p. 141 C. to 142 C.

Step D.Preparation of 2-cyano-5-morpholino-N-isopropylaniline: A mixture of 5.4 g. of 2-cyano-5-morpholinoaniline and 5 g. of anhydrous sodium carbonate in 20 ml. of isopropyl iodide is heated under reflux for 96 hours. The mixture is then cooled, diluted with 100 ml. of ether and filtered. The filtrate is washed with water and dried. Removal of the ether gives a residue which is crystallized from ethanol to obtain 2-cyano-5-morpholino-N- isopropylaniline, m.p. 121 C. to 123 C.

Step E.Preparation of 2-isopropy1amino-4-morpholino-benzophenonimine: A solution of 4.9 g. of 2-cyano-5- morpholino-N-isopropylaniline in 100 ml. of absolute ether is added dropwise to a stirred solution of 60 millimoles of phenyllithium in a 50/50 mixture of diethyl ether and benzene 0-5 C. Stirring is continued for 1 hour while the mixture is allowed to warm to room temperature. It is then poured onto ice/water and the organic phase is separated. After drying over anyhdrous sodium sulfate the solvent is removed in vacuo to obtain 2- isopropylamino-4-morpholino benzophenonirnine as a crude oil.

Step F.-Preparation of 1-isopropyl-7-morpholino-4- phenyl-2(1H)'q11inazolinone: To a mixture of 4 g. of crude 2-isopropylamino-4-morpholinobenzophenonimine and 5 ml. of triethylamine in 30 ml. of benzene, cooled to a temperature of 10 C. is added 25 ml. of 12% solution of phosgene in benzene. The resulting mixture is allowed to stand at room temperature for 1% hours and then gently warmed in vacuo to remove excess phosgene. The residue is washed with 2N sodium hydroxide solution and the organic phase is separated, dried and evaporated in vacuo to obtain an oil that is crystallized from a mixture of diethyl ether/methylene chloride in a ratio of about 3/1 to obtain 1-isopropyl-7-morpholino-4-phenyl-2(1H)- quinazolinone, m.p. C. to 176 C.

This product may be readily converted to the hydrochloride acid addition salt which is crystallized from ethanol/diethyl ether to obtain 1-isopropyl-7-morpholino- 4-phenyl-2(1H)-quinazolinone hydrochloride, m.p. 188 C. to 192 C. (decomp).

EXAMPLE 2 l-isopropyl-6-morpholino-4-phenyl-2( 1H)-quinazolinone Step A.Preparation of -nitro2-isopropylaminobenzophenone: A mixture of g. of 5-nitro-2-chlorobenzophenone, 700 mg. of powdered copper, 700 mg. of cuprous chloride, 15 ml. of ethanol, and 15 ml. of liquid isopropylamine is refluxed for hours. The reaction mixture is then worked up in a conventional manner to obtain a residue which is crystallized from ethanol to give yellow prisms of 5-nitro-2-isopropylaminobenzophenone, m.p. 155 C.

Step B.-Preparation of 6-nitro-1-isopropyl-4-phenyl- 2(1H)-quinazolinone: Employing substantially the procedure of Example 3 (Step B), hereinafter, and employing equivalent amounts, the residue of the organic phase is crystallized from ethyl acetate to give yellow prisms of 6- nitro-1-isopropyl-4 phenyl 2(1H) quinazolinone, m.p. 190-192" C.

Step C.-Preparation of 6-amino-l-isopropyl-4-phenyl- 2(1H)-quinazolinone: A solution of 12.0 g. of 6-nitro-lisopropyl-4-phenyl-2(1H)-quinazolinone dissolved in 240 ml. of hot ethanol is heated to boiling and with stirring there is added 80 ml. of water, and then 16 g. of iron filings. There is than also added dropwise with stirring a solution made up of 80 ml. ethanol, 20 ml. water and 4 ml. 2N hydrochloric acid over the course of 40 minutes. The resulting mixture is refluxed for 3 hours, and there is then added to the hot solution 4 ml. of 2N sodium hydroxide followed by filtering and concentration in vacuo to remove most of the ethanol. There is added to the concentrate 100 ml. of ethyl acetate followed by extraction of the organic phase 3 times each with 50 ml. of dilute hydrochloric acid. The aqueous phases are combined and made alkaline with sodium hydroxide followed by 2 extractions each with 100 ml. of methylene chloride. The organic phases are combined and dried over anhydrous sodium sulfate, filtered and evaporated in vacuo to dryness. The residue is crystallized from ethyl acetate to obtain yellow prisms of 6-amino-1-isopropyl-4-phenyl- 2(1H)-quinazolinone, m.p. 210-215 C.

Step D. Preparation of l-isopropyl-6-morpholino-4- phenyl-2(1H)-quinazolinone: A mixture of 4 g. of 1 isopropyl 6 amino 4-phenyl-2(1H)-quinazolinone and 4 g. of anhydrous potassium carbonate in 20 ml. of bis- (2-bromoethyl)ether is heated and stirred at 140 C. for 1 /2 hours. The excess reagent is then removed in vacuo and the residue is distributed between methylene chloride and ice cold 2N sodium hydroxide solution. The organic phase is separated washed with water and dried Removal of the solvent gives a crude oily product which is dissolved in ethanol and gaseous hydrogen chloride is passed through to precipitate the hydrochloride salt. This salt is isolated by filtration and shaken with methylene chloride/ 2N sodium hydroxide solution to re-isolate the free base. The organic phase is separated, dried and evaporated to give a residue which on crystallization from diethyl ether yields 1 isopropyl 6 morpholino-4-phenyl-2(1H)- quinazolinone, m.p. 172-175 C.

EXAMPLE 3 1-isopropyl-7-methyl-6-morpholino-4-phenyl-2( 1H) quinazolinone CH5 CH3 Step A.Preparation of 4-methyl-2-isopropylaminobenzophenone: A mixture of 7 g. of 4-methyl-2-aminobenzophenone, 6.35 g. of sodium carbonate and 18.8 ml. of 2-iodopropane is stirred and refluxed for 3 days. The cooled reaction mixture is then diluted with 200 ml. of benzene and washed twice with water and twice with brine. The organic phase is separated, dried over anhydrous sodium sulfate and concentrated in vacuo to remove substantially all of the benzene. The resulting yellow oil is dissolved in about 10 ml. of methylene chloride and subjected to column chromatography employing alumina (about 400 g.) and methylene chloride as eluant to give a first fraction which on concentration in vacuo to remove methylene chloride produced a yellow oil of 4-methyl-2-isopropylaminobenzophenone.

Step B.Preparation of l-isopropyl-7-methyl-4-phenyl- 2(1H)-quinazolinone: A mixture of 5.9 g. of 4-methyl-2- isopropylaminobenzophenone prepared in Step A above, 13.9 g. of urethane and 500 milligrams of zinc chloride is heated at a temperature of 190 C. for 1 /2 hours. There is then additionally added 7 g. of urethane and 250 milligrams of zinc chloride, and the heating continued at a temperature of 190 C. for an additional 2% hours. The resulting mixture is cooled to about C. and diluted with chloroform. The resulting mixture is then filtered and the filtrate Washed first with water and then with brine. The organic phase is separated, dried over anhydrous sodium sulfate and concentrated in vacuo to remove substantially all of the chloroform and obtain an oily residue which is dissolved in a small amount of about 20 ml. of methylene chloride. The resulting solution is then diluted with about 40 m1. of ethyl acetate and concentrated in vacuo to crystallize 1-isopropy1-7-methyl-4- phenyl-2(lH)-quinazolinone; m.p. 137 to 138 C.

Step C.Preparation of 1-isopropyl-7-methyl-6-nitro- 4-phenyl-2(1H)-quinazolinone: To a cooled solution (0.5 C.) of 13.9 g. of 1-isopropyl-7-methyl-4-phenyl- 2(1H)-quinazolinone in 50 ml. of concentrated sulfuric acid is added dropwise over 10 minutes a solution of 6.07 g. of potassium nitrate in 15 ml. of concentrated sulfuric acid. The resulting solution is allowed to warm to room temperature and then stirred for 2 hours. The solution is then poured into ice water and the resulting solid is isolated by filtration. The solid is dissolved in 100 ml. of diethyl ether and the solution is washed once with 100 ml. of water before being dried over anhydrous sodium sulfate. The mixture is filtered and the filtrated is evaporated in vacuo to yield a residue which is crystallized from 50 ml. of ethyl acetate to obtain 1-isopropyl-7- methyl-6-nitrio-4-phenyl-2(1H)quinazolinone, m.p. 192- 194 C.

Step D.Preparation of 6-amino-1-isopropy1-7-methyl- 2-phenyl-2(1H)-quinazolinoue: A mixture of 7.5 g. of 1- isopropyl-7-methyl-6-nitro-4-phenyl 2(1H) quinazolinone and about 9 g. of Raney nickel sludge in water in 50 ml. of dioxane is shaken at room temperature under a hydrogen pressure of 50 p.s.i. for 5 hours. The reaction mixture is then filtered through Celite, the filtrate is evaporated to dryness, and the residue crystallized from 9 ethyl acetate to obtain 6-amino-1-isopropyl-7-methyl-4- phenyl-2(1H)-quinazolinone, m.p. 193-196 C.

Step E.-Preparation of 1-isopropyl-7-methyl-6-morpholino-4-phenyl-2(1H)-quinazolinone: A mixture of 7.5 g. of 6 amino 1-isopropyl-7-methyl-4-phenyl-2(1H)- quinazolinone and 1.5 g. of anhydrous potassium carbonate in 8 ml. of bis(2-bromoethyl)ether is heated and stirred at 120 C. for 24 hours. The mixture is worked up as described in Example 2 (Step D) to obtain on crystallization from ethyl acetate/diethyl ether (10:1) the compound 1 isopropyl 7 methyl-6-morpholino- 4-phenyl-2(1H)-quinazolinone, m.p. 218-221 C.

The word lower as used herein in association with such terms as lower alkyl, lower alkoxy, and the like shall be taken as indicating an organic substituent of from 1 to 6 carbon atoms, inclusive, unless otherwise defined herein.

What is claimed is:

1. A compound of the formula RI 6 N wherein R is hydrogen, halo of atomic weight no greater than 80, alkyl of 1 to 3 carbon atoms or alkoxy of 1 or 2 carbon atoms,

R is alkyl of 1 to 5 carbon atoms, allyl, metallyl or propargyl,

R" is phenyl or substituted phenyl of the formula Y is halo of atomic weight no greater than 80, alkyl of l to 3 carbon atoms, alkoxy of 1 or 2 carbon atoms or trifluoromethyl, and

Y is hydrogen, halo of atomic weight no greater than 80, alkyl of 1 to 3 carbon atoms or alkoxy of 1 or 2 carbon atoms.

2. A compound of claim 1 in which -R is hydrogen.

3. A compound of claim 2 in which R" is phenyl.

4. A compound of claim 2 in which R is isopropyl.

5. The compound of claim 4 which is 2-isopropylamino-4-morpholinobenzophenonimine.

References Cited UNITED STATES PATENTS Re. 26,655 8/ 1969 Sherlock et al. 260-2955 R 3,454,587 7/1969 Littell et a1. 260-2955 3,708,481 1/1973 Hoffmann 260-2472 B DONALD G. DAUS, Primary Examiner J. TOVAR, Assistant Examiner US. Cl. X.R. 

